Pałucha Agnieszka, Brański Piotr, Kĺak Kinga, Sowa Magdalena
Department of Neurobiology, Institute of Pharmacology Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland.
Pharmacol Rep. 2007 Sep-Oct;59(5):525-30.
An increasing body of evidence indicates an important role of the glutamatergic system in the pathophysiology of depression. Not only ionotropic but also metabotropic glutamate receptors (mGlu receptors) have been suggested to be involved in the mechanism of action of antidepressant drugs. Moreover, several mGlu receptor ligands possess a great antidepressant potential. Group II mGlu receptor antagonists have been shown to induce antidepressant-like effects in rodents. An influence of chronic antidepressant treatment on group II mGlu receptors has also been suggested. In our studies, we examined an influence of repeated (21-day) imipramine treatment on the density of group II mGlu receptors and affinity of mGlu2 and mGlu3 receptor radioligand [3H]-LY341495 for group II mGlu receptors in the rat brain hippocampus and frontal cortex. Moreover, we analyzed an influence of chronic imipramine administration on the ability of group II mGlu receptor agonist, 2R,4R-APDC, to inhibit forskolin-stimulated cAMP accumulation in the rat brain cortical slices. We found that inhibitory properties of group II mGlu receptors were diminished after chronic, but not acute imipramine administration. However, no changes in the density or affinity of the mGlu2 and mGlu3 receptor ligand for group II mGlu receptors were observed.
越来越多的证据表明谷氨酸能系统在抑郁症的病理生理学中发挥重要作用。不仅离子型谷氨酸受体，而且代谢型谷氨酸受体（mGlu受体）也被认为参与了抗抑郁药物的作用机制。此外，几种mGlu受体配体具有很大的抗抑郁潜力。II组mGlu受体拮抗剂已被证明在啮齿动物中可诱导出抗抑郁样效应。也有人提出慢性抗抑郁治疗对II组mGlu受体有影响。在我们的研究中，我们检测了重复（21天）给予丙咪嗪对大鼠脑海马和额叶皮质中II组mGlu受体密度以及mGlu2和mGlu3受体放射性配体[3H]-LY341495与II组mGlu受体亲和力的影响。此外，我们分析了慢性给予丙咪嗪对II组mGlu受体激动剂2R,4R-APDC抑制大鼠脑皮质切片中福司可林刺激的cAMP积累能力的影响。我们发现，慢性而非急性给予丙咪嗪后，II组mGlu受体的抑制特性减弱。然而，未观察到mGlu2和mGlu3受体配体与II组mGlu受体的密度或亲和力发生变化。
